Abstract 55: High frequency of TP53 mutations in canine skin tumors recapitulates solar induced human lesions representing an important research model of spontaneous diseases
Authors: Lucas Rodrigues, Thaynan Vieira, Garrett Harvey, Dorothy Girimonte, Gerald Post, Lindsay Lambert, Aubrey Miller, Abigail Hull, Chase Schwalbach, Christina Lopes, Michelle White
Journal: Cancer Research (2023)

Abstract Skin tumors are the most common type of neoplastic lesion affecting humans and dogs, and their incidence is increasing for both species. Skin tumor initiation and progression are associated with chronic exposure to ultraviolet (UV) radiation, mainly for light-skinned individuals, that can activate different oncogenes and pathways. Solar UV-induced mutations, characterized by C to T or CC to TT mutations, are well described in the TP53 gene in human skin cancers such as ​​basal cell carcinoma, squamous cell carcinoma and melanoma. This study evaluated TP53 mutations in 2201 canine tumors enrolled in FidoCure Precision Medicine Platform. Tumors were classified in 26 different types according to their histology and anatomic location. Gastrointestinal tumors, insulinomas and mesotheliomas did not carry any TP53 mutation as opposed to cutaneous squamous cell carcinoma (CSCC) and cutaneous hemangiosarcoma (CHSA) that had higher number of TP53 mutations in 88.9% and 77.8% of cases, respectively. Canine CSCC had a similar frequency of TP53 mutations compared to humans, previously identified in 83.64% of cases (MSKCC, Nat Med 2017). The C to T transitions were the most prevalent type of mutations in both canine CSCC and CHSA representing 66.67% and 55.55% of TP53 mutations, respectively. On the other hand, C&amp;gt;T corresponded to just 23.36% of TP53 mutations for the other 24 tumor types. R261H, G290R, R184*, S229F, N143K and R201* variants were identified more than 10 times in all canine tumors. Canine CSCC and CHSA were enriched with R201* (P&amp;lt;0.0001; P=0.004) and R184*(P&amp;lt;0.0001; P=0.048). These two nonsense variants are C&amp;gt;T changes at the position 601 and 550, respectively. They are homologous to human R213* (637C&amp;gt;T) and R196* (586C&amp;gt;T). Canine R201* was identified in 44.4% of CSCC, and human R213* in 73.91% of cases (MSKCC, Nat Med 2017). This study identified a high frequency of TP53 mutations in canine cutaneous tumors consistent with solar induced lesions. These results position canines as excellent spontaneous models of human solar induced cancers that can be utilized to elucidate elements of cancer biology, prognosis and responses across a wide spectrum of therapies. Citation Format: Lucas Rodrigues, Thaynan Vieira, Garrett Harvey, Dorothy Girimonte, Gerald Post, Lindsay Lambert, Aubrey Miller, Abigail Hull, Chase Schwalbach, Christina Lopes, Michelle White. High frequency of TP53 mutations in canine skin tumors recapitulates solar induced human lesions representing an important research model of spontaneous diseases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 55.